Disturbances of the inner ear fluids are responsible for a number of clinical disorders. The proposed studies focus on the relationships between endolymph volume disorders and inner ear function. Physiologic measures have been developed that are sensitive to small endolymph volume disturbances even when cochlear sensitivity is not impaired. They are based on even-order distortions (second harmonic (2f), f2-f1 and f2+f1 emissions) that change when the organ of Corti is displaced from its normal resting position, thereby altering hair cell transduction properties. Cochlear transducer "operating point" can be derived from cochlear microphonic and from less-invasive acoustic emissions recordings. The interrelationships between distortions and operating point will be characterized during manipulations that disturb operating point or endolymph volume. Results will be compared with models that predict the dependence of distortion on operating point. The ability to document abnormal endolymph volume states through acoustic emissions recordings is clinically relevant as it may allow endolymphatic hydrops to be diagnosed. Techniques for manipulating inner ear fluids in a minimally invasive manner will also be investigated. The distribution of drugs in the cochlea will be quantified following their application to the round window membrane with a variety of protocols. Novel perilymph sampling techniques will be used to document longitudinal drug gradients in the cochlea. Models of drug distribution in the ear will be refined and used to predict drug distribution patterns in the human ear. 3-D models will be compared with our existing simulations of inner ear fluids. Physiologic changes associated with endolymph volume disturbance and recovery will be measured. Treatments will be screened that could potentially influence endolymph volume. The findings from these combined studies are expected to directly impact both the diagnosis and management of Meniere's disease.